Interfering RNA molecules
The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.
1. A double stranded siRNA molecule against a target nucleic acid, wherein the double stranded siRNA molecule comprises a first strand and a second strand, wherein the first strand comprises a first stretch that is complementary to the target nucleic acid, wherein the second strand comprises a second stretch that has the same length as the first stretch and is complementary to the first stretch, wherein the first strand and the second strand form a double-stranded structure comprising the first stretch and the second stretch, wherein the first stretch and the second stretch each has the length of 17-21 nucleotides, wherein the first stretch and the second stretch each comprises a plurality of groups of 2′-O-methyl ribonucleotides flanked on one or both sides by a flanking group of unmodified ribonucleotides or modified ribonucleotides different from 2′-O-methyl ribonucleotides, and wherein the number of 2′-O′methyl ribonucleotides in at least one of the plurality of groups of 2′-O-methyl ribonucleotides is ten.
2. The double stranded siRNA molecule of claim 1 , wherein at least one of the flanking groups of the unmodified ribonucleotides or modified ribonucleotides different from 2′-O-methyl ribonucleotides comprises one or more 2′-fluoro ribonucleotides.
3. The double stranded siRNA molecule of claim 2 , wherein each 2′-fluoro ribonucleotide on the first stretch corresponds to a 2′-O-methyl ribonucleotide on the second stretch.
4. The double stranded siRNA molecule of claim 2 , wherein each 2′-fluoro ribonucleotide on the second stretch corresponds to a 2′-O-methyl ribonucleotide on the first stretch.
5. The double stranded siRNA molecule of claim 3 , wherein each 2′-fluoro ribonucleotide on the second stretch corresponds to a 2′-O-methyl ribonucleotide on the first stretch.
6. The double stranded siRNA molecule of claim 1 , wherein the 3′-end of the first strand has an overhang.
7. The double stranded siRNA molecule of claim 6 , wherein the overhang has two nucleotides.
8. The double stranded siRNA molecule of claim 1 , wherein the 5′-end of the first strand and 3′-end of the second strand is blunt ended.
9. The double stranded siRNA molecule of claim 6 , wherein the 5′-end of the first strand and 3′-end of the second strand is blunt ended.
10. The double stranded siRNA molecule of claim 7 , wherein the 5′-end of the first strand and 3′-end of the second strand is blunt ended.
11. The double stranded siRNA molecule of claim 5 , wherein the 3′-end of the first strand has an overhang, and wherein the 5′-end of the first strand and 3′-end of the second strand is blunt ended.
12. The double stranded siRNA molecule of claim 11 , wherein the overhang has two nucleotides.
13. The double stranded siRNA molecule of claim 1 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
14. The double stranded siRNA molecule of claim 1 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
15. The double stranded siRNA molecule of claim 2 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
16. The double stranded siRNA molecule of claim 2 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
17. The double stranded siRNA molecule of claim 5 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
18. The double stranded siRNA molecule of claim 5 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
19. The double stranded siRNA molecule of claim 9 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
20. The double stranded siRNA molecule of claim 9 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
21. The double stranded siRNA molecule of claim 10 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
22. The double stranded siRNA molecule of claim 10 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
23. The double stranded siRNA molecule of claim 11 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
24. The double stranded siRNA molecule of claim 11 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
25. The double stranded siRNA molecule of claim 12 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
26. The double stranded siRNA molecule of claim 12 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
27. The double stranded siRNA molecule of claim 25 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is less than the number of 2′-O-methyl ribonucleotides on the second stretch.
28. The double stranded siRNA molecule of claim 1 , wherein the target nucleic acid is selected from the group consisting of structural genes, housekeeping genes, transcription factors, motility factors, cell cycle factors, cell cycle inhibitors, enzymes, growth factors, cytokines, and tumor suppressors.
29. A composition comprising the double stranded siRNA molecule of claim 1 .
30. The composition of claim 29 , wherein the composition is a pharmaceutical composition.